Liver fibrosis is a global health problem and one of the leading causes of morbidity and mortality in western developed countries. Liver fibrosis may be caused by chronic liver damage, such as hepatitis, alcohol abuse, and nonalcoholic steatohepatitis. Regardless of its cause, liver fibrosis is characterized by the excessive accumulation of extracellular matrix (“ECM”) in the liver. HSCs are the main producers responsible for the excessive production of ECM and profibrogenic cytokines in fibrotic liver. Therefore, development of HSC-specific delivery systems is essential for the success of antifibrotic agents.
The insulin-like growth factor 2 receptor (“IGF2R”), also known as cation-independent mannose-6-phosphate receptor (M6PR), is a member of the IGF signaling system. IGF2R is a 300 kDa glycoprotein containing three domains, the cytoplasmic domain, transmembrane domain, and extracellular domain. The major function of IGF2R is to regulate lysosomal enzymes such as growth factor IGF2 by transporting them into lysosomes, followed by digestion by lysosomal acid hydrolases. IGF2R is expressed in HSCs, and its expression is upregulated during liver fibrogenisis. Moreover, IGF2R can internalize extracellular ligands, and therefore it can be adopted as a target receptor for HSC-specific drug delivery.
Conventional methods for delivering drugs to HSCs have limitations including inefficient uptake. Recently, drug delivery systems have utilized peptides because of their high binding affinity, ease of syntheses, and the ability to identify peptides that target specific proteins, cells, and tissues. Nevertheless, no peptides have been identified to specifically target IGF2R. Therefore, there is a need to identify IGF2R-specific peptides that can be used in various applications which target IGF2R.